Our long term goal is to decipher the molecular mechanisms that mediate cell growth, proliferation and differentiation. The central theme of this program project is firmly rooted in the conviction that transcriptional regulation provides the key link in triggering the complex cellular processes require to initiate cell growth. Project 5 "Control of cellular proliferation by cAMP": This program proposes to dissect the molecular mechanism by which cAMP can act both as an inhibitor and mitogen for cell proliferation. Project 6 "Activation of TCR alpha-chain enhancer by the LEF-1 HMG protein": The aim of this project is to define the molecular mechanisms involved in the transcription of alpha chain of T cell receptor (TCR alpha) gene. Project 3 "Transcriptional regulation of T cell receptor alpha gene": Experiments are proposed to study how TCR alpha gene is transcriptionally regulated during T-lymphocyte development, with particular focus on the role of enhancer sequences which lie at a distance of 69 kb. Project 7 "Proto-oncogene signalling pathways and steroid hormone receptors": This proposal is to understand the molecular mechanisms by which glucocorticoids and retinoids repress transcription by early response genes like Fos, Jun and NF-kappaB/Rel. Project 8 "Structural analysis of cell growth regulators": The three-dimensional structure of receptor phospho tyrosine phosphatase alpha (RPTPalpha) and IkappaBalpha or p65/IkappaBalpha will be determined. In addition to the seven projects, there are three core facilities. Core 9001 "Peptide synthesis and antibody production": This core will be involved in synthesis of peptides and generation of antibodies. Core 9002 "Characterization of proteins and their post-translational modifications": This core will be responsible for determining primary amino acid sequences.